Cases Of Cervical Intraepithelial Neoplasia Research Articles

Prospective seroepidemiologic study on the role of Human Papillomavirus and other infections in cervical carcinogenesis: Evidence from the EPIC cohort

To evaluate prospectively the association between serological markers of selected infections, including HPV, and risk of developing cervical cancer (CC) and precancer, we performed a nested case-control study within the European Prospective Investigation into Cancer and Nutrition (EPIC) study that included 184 cases of invasive CC (ICC), 425 cases of cervical intraepithelial neoplasia (CIN) grade 3 or carcinoma in situ (CIS), and 1,218 matched control women. At enrollment participants completed lifestyle questionnaires and provided sera. Subjects were followed-up for a median of 9 years. Immunoassays were used to detect serum antibodies to Human Herpes Virus 2 (HHV-2), Chlamydia trachomatis (CT), Chlamydia pneumoniae, L1 proteins of mucosal and cutaneous HPV types, E6/E7 proteins of HPV16/18, as well as to four polyomaviruses. Adjusted odds ratios (OR) [and 95% confidence intervals (CI)] for CIN3/CIS and ICC risk were respectively: 1.6 (1.2-2.0) and 1.8 (1.1-2.7) for L1 seropositivity to any mucosal HPV type, 1.0 (0.4-2.4) and 7.4 (2.8-19.7) for E6 seropositivity to HPV16/18, 1.3 (0.9-1.9) and 2.3 (1.3-4.1) for CT seropositivity, and 1.4 (1.0-2.0) and 1.5 (0.9-2.6) for HHV-2 seropositivity. The highest OR for ICC was observed for HPV16 E6 seropositivity [OR = 10.2 (3.3-31.1)]. Increasing number of sexually transmitted infections (STIs) was associated with increasing risk. Non-STIs were not associated with CC risk. In conclusion, this large prospective study confirms the important role of HPV and a possible contribution of CT and HHV-2 in cervical carcinogenesis. It further identifies HPV16 E6 seropositivity as the strongest marker to predict ICC well before disease development.

P53 and bcl2 expression in malignant and premalignant lesions of uterine cervix and their correlation with human papilloma virus 16 and 18

Background and Objective:Persistent high risk human papilloma virus (HPV) infection is probably the best predictor of increased risk of cervical cancer, but expression of certain markers of cell proliferation and apoptosis have been studied. The present study was conducted to evaluate the expression of p53 and bcl2 in premalignant and malignant lesions of cervix and its correlation with HPV type 16 and 18.Materials and Methods:The study comprised of 35 cases (including 24 prospective cases and 11 retrospective cases) of premalignant and malignant lesions of the cervix. Slides were stained with Hematoxylin and Eosin and p53, bcl2 (immunohistochemistry), HPV 16 and HPV 18 (in situ hybridization).Results:p53 positivity was seen in 8/19 (42.1%) cases of cervical intraepithelial neoplasia (CIN) and 8/16 (50%) cases of carcinoma cervix, the difference not significant statistically. The difference in bcl2 expression in CIN versus carcinoma cervix (84.21% vs. 43.75%) was statistically significant (P = 0.030). There was no significant difference between p53 and bcl2 expression and the stage and grade of the tumors. Seven out of 19 cases of CIN (36.84%) were positive for HPV 16/18 infection and 8/16 cases (50%) of carcinoma cervix were HPV positive (P = 0.628).Conclusions:No significant association was found between HPV 16/18 infection and p53 and bcl2 expression in premalignant and malignant lesions of uterine cervix. Although, bcl2 staining showed a significant difference between CIN and carcinoma cervix, a larger case series is required to assess the association between HPV infection and overexpression of p53 and bcl2 proteins in these lesions.

An immunohistochemical analysis of sex-steroid receptors, tumor suppressor gene p53 and Ki-67 in the normal and neoplastic uterine cervix squamous epithelium.

Malignant transformation of sex-steroid dependent tissues is associated with the loss of expression of sex steroid receptors as well as of the tumor suppression gene p53. The aim of this study is to evaluate the expression of sex-steroid receptors, p53 and Ki-67 in specimens from pre-malignant and malignant cervical epithelial lesions throughout the menstrual cycle. Immunohistochemical staining was performed on formalin fixed, paraffin embedded tissue sections of normal squamous cervical epithelium, cervical intraepithelial neoplasia and invasive squamous cervical carcinoma, specimens utilizing antibodies against estrogen receptors, progesterone receptors, p53 protein and Ki-67 antigen. In the samples taken from the normal cervical tissue, basal cells were usually estrogen receptor-positive, progesterone receptor-negative, p53-negative and Ki-67-negative throughout the menstrual cycle. In contrast, para-basal cells were estrogen receptor-positive and progesterone receptor-negative in the follicular phase, but estrogen receptor-negative and progesterone receptor-positive and Ki-67 positive in the luteal phase. In cervical precancerous and cancer tissue samples (cervical intraepithelial neoplasia and squamous cervical carcinoma), the expression of estrogen receptors decreased. 31.15% of cervical intraepithelial neoplasia and 11.5% of squamous cervical carcinoma were positive for estrogen receptors. However, the expression of progesterone receptors increased. 29.5% of cervical intraepithelial neoplasia and 49.2% of squamous cervical carcinoma were positive for progesterone receptors. Positive staining for p53 was observed in 15 (24.59%) cases of cervical intraepithelial neoplasia and in 39 (64%) of squamous cervical carcinoma. The expression Ki-67 index in squamous cervical carcinoma cases (47.60%) was significantly higher than of cervical intraepithelial neoplasia cases (30.2%) (p = 0.041). The findings of this study suggest that tumor cervical cells evade normal growth control by sex steroid hormones while synchronously abnormal regulatory mechanisms acquire control of the cell cycle.

High expression of ezrin predicts poor prognosis in uterine cervical cancer

BackgroundEzrin, a member of the ezrin/radixin/moesin (ERM) protein family, plays a pivotal role in tumor invasion and metastasis. This study is aimed to investigate the clinicopathological significance of upregulated ezrin protein expression in uterine cervical cancers.MethodsImmunohistochemical staining of ezrin protein was performed on uterine cervical cancer specimens from 235 patients. For comparison, 239 cases of cervical intraepithelial neoplasia (CIN), 17 cases of cervical glandular intraepithelial neoplasia (CGIN) and 52 normal cervix samples were also included. qRT-PCR was performed on fresh tissues to detect ezrin mRNA expression levels. HPV infection statuses were genotyped by oligonucleotide microarray, and 10-year survival rates were calculated using the Kaplan-Meier method for 109 cervical cancer patients.ResultsApical membranous distribution of ezrin protein was only observed in normal cervical glands, while perinuclear staining was only observed in cervical cancers. Strong cytoplasmic and diffuse localization of ezrin were frequently seen in the cervical cancers compared with the normal counterparts. Furthermore, this strongly positive ezrin expression was significantly higher in cervical cancers than in CIN, CGIN, and normal cervical epithelia. Ezrin overexpression was closely related with poor differentiation, late stage, and lymph node metastasis. Additionally, ezrin overexpression was associated with lower 10-year survival rate for patients with early stage cervical cancer, but not for patients with advanced stage.ConclusionsAberrant localization and overexpression of ezrin might be an independent effective biomarker for prognostic evaluation of cervical cancers.

Human papillomavirus, high-grade intraepithelial neoplasia and killer immunoglogulin-like receptors: a Western Australian cohort study

BackgroundHuman papillomavirus (HPV) is the causative agent in cervical cancer and HPV genotypes 16 and 18 cause the majority of these cancers. Natural killer (NK) cells destroy virally infected and tumour cells via killer immunoglobulin-like receptors (KIR) that recognize decreased MHC class I expression. These NK cells may contribute to clearance of HPV infected and/or dysplastic cells, however since KIR controls NK cell activity, KIR gene variation may determine outcome of infection.MethodsKIR gene frequencies were compared between 147 patients with a history of high-grade cervical intraepithelial neoplasia (CIN) and a control population of 187, to determine if any KIR genes are associated with high-grade CIN. In addition a comparison was also made between cases of high grade CIN derived from 30 patients infected with HPV 16/18 and 29 patients infected with non-16/18 HPV to determine if KIR variation contributes to the disproportional carcinogenesis derived from HPV 16/18 infection.ResultsHigh-grade CIN was weakly associated with the absence of KIR2DL2 and KIR2DS2 (p = 0.046 and 0.049 respectively, OR 0.6; 95% CI 0.4 – 0.9) but this association was lost after correction for multi-gene statistical analysis. No difference in KIR gene frequencies was found between high-grade CIN caused by HPV 16/18 and non-16/18.ConclusionNo strong association between KIR genes, high-grade CIN and HPV genotype was found in the Western Australian population.

Application of Human Papillomavirus in Screening for Cervical Cancer and Precancerous Lesions

Cervical cancer is a commonly-encountered malignant tumor in women. Cervical screening is particularly important due to early symptoms being deficient in specificity. The main purpose of the study is to assess the application value of cervical thinprep cytologic test (TCT) and human papillomavirus (HPV) detection in screening for cervical cancer and precancerous lesions. In the study, cervical TCT and HPV detection were simultaneously performed on 12,500 patients selected in a gynecological clinic. Three hundred patients with positive results demonstrated by cervical TCT and/or HPV detection underwent cervical tissue biopsy under colposcopy, and pathological results were considered as the gold standard. The results revealed that 200 out of 12,500 patients were abnormal by TCT, in which 30 cases pertained to equivocal atypical squamous cells (ASCUS), 80 cases to low squamous intraepithelial lesion (LSIL), 70 cases to high squamous intraepithelial lesion (HSIL) and 20 cases to squamous cell carcinoma (SCC). With increasing pathological grade of cervical biopsy, however, TCT positive rates did not rise. Two hundred and eighty out of 12,500 patients were detected as positive for HPV infection, in which 50 cases were chronic cervicitis and squamous metaplasia, 70 cases cervical intraepithelial neoplasia (CIN) I, 60 cases CIN II, 70 cases CIN III and 30 cases invasive cervical carcinoma. Two hundred and thirty patients with high-risk HPV infection were detected. With increase in pathological grade, the positive rate of high-risk HPV also rose. The detection rates of HPV detection to CIN III and invasive cervical carcinoma as well as the total detection rate of lesions were significantly higher than that of TCT. Hence, HPV detection is a better method for screening of cervical cancer at present.

Abstract 4251: Genomewide methylation and expression profiles in cervical cancer.

Abstract Cervical carcinoma is one of the most common cancers in females. This cancer begins with precancerous stages and can evolves to carcinoma over 10 years or more. Cervical cancer is a multistep process with accumulation of genetic and epigenetic alterations in regulatory genes, leading to activation of oncogenes and inactivation or loss of tumor suppressor genes. We aimed to identify genetic alterations associated with pre-cancerous stage and also with cervical cancer. For this purpose, microarray comparative genomic hybridization(Illumina 450K and Illumina Expression HT12 Human CGH Whole-Genome Arrays) was performed with 16 cases of cervical intraepithelial neoplasia(CIN) of different stages and 3 cases of carcinoma. We identified epigenetic inactivation of TSGs by hyper- or hypo-methylation which has been recognized as an important and alternative mechanism in tumorigenesis. Here we discuss these epigenetic alterations in cervical intrapeithelial neoplasia and cervical cancer focusing on DNA methylation. Citation Format: Kwon Yongil, Nakwoo Lee, Sungjong Lee. Genomewide methylation and expression profiles in cervical cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4251. doi:10.1158/1538-7445.AM2013-4251

MTHFR C677T polymorphism was an ethnicity-dependent risk factor for cervical cancer development: evidence based on a meta-analysis.

Many studies have studied the associations between 5, 10-methylene tetrahydrofolate reductase (MTHFR) polymorphisms and susceptibilities of cervical cancer and cervical intraepithelial neoplasia (CIN); however, the results were inconsistent. The aim of this study was to further assess the relationships by the method of meta-analysis. Two investigators independently searched the PubMed, Embase, Wang Fang (Chinese database) and CNKI (China National Knowledge Infrastructure), with latest update to July 1st, 2011. The pooled odds ratio (OR) and 95 % confidence interval (95 % CI) were used to assess the strength of the associations by using fixed- or random-effect model. Ten case-control studies were included in this meta-analysis including a total of 1,803 cervical cancer or CIN cases and 2,363 controls. Pooled analyses showed that T allele of MTHFR C677T was significantly associated with increased CIN risk [OR (95 % CI): 1.28 (1.03-1.50) for CT vs. CC], especially for low-grade CIN risk. In addition, MTHFR C677T rather than A1298C polymorphism was associated with risk of cervical cancer. Stratifying analyses for ethnicity indicated that T allele of MTHFR C677T was associated with increased cervical cancer risk for Asian [OR (95 % CI): 1.56 (1.17-2.08) for TT vs. CC; 1.53 (1.19-1.96) for TT vs. C carriers] while decreased risk for Caucasian [OR (95 % CI): 0.63 (0.45-0.89) for TT vs. CC; 0.66 (0.56-0.79) for T carriers vs. CC]. This meta-analysis suggested that there was no association between MTHFR A1298C polymorphism and cervical cancer risk. However, MTHFR C677T was an ethnicity-dependent risk factor for cervical cancer occurrence. In addition, T allele of C677T was significantly associated with risk of low grade of CIN incidence. Because of modest limitations of our study, well-designed studies with large sample size were needed to confirm our findings in the future.

Cost and Effectiveness Comparison of Immediate Colposcopy Versus Human Papillomavirus DNA Testing in Management of Atypical Squamous Cells of Undetermined Significance in Turkish Women

A small but significant proportion of cases with atypical squamous cells of undetermined significance (ASCUS) may harbour CIN 2-3, or even invasive carcinoma. Although immediate colposcopy, HPV-DNA testing or expectant management are three recommended options in ASCUS triage, a consensus does not currently exist on which one of these approaches is the most efficient. In this study, we aimed to compare the performance and cost of immediate colposcopy and colposcopy based on the human papillomavirus (HPV) testing for detecting histologically confirmed high-grade cervical intraepithelial neoplasia (CIN) in women with ASCUS. Records of 594 women with an index Papanicolaou smear showing ASCUS were retrospectively analyzed. Women in the immediate colposcopy arm were referred directly to colposcopy (immediate colposcopy group, n=255) and those in the HPV triage arm were proceeded to colposcopy if the high-risk HPV (hrHPV) test was positive (HPV triage group, n=339). High grade CIN (CIN2+) detection rate and treatment costs were compared between the groups. The detected rate of CIN2+ was higher in the HPV triage group compared to immediate colposcopy group (8% vs. 1.6%, p=0.011). In the HPV triage group, the total cost, cost per patient, and the cost for detecting one case of high grade CIN were higher than the immediate colposcopy group (p<0.001). In women with ASCUS cytology, HPV DNA testing followed by colposcopy is more costly than immediate colposcopy, but this approach is associated with a higher rate of CIN2+ detection. This findings suggest that HPV DNA testing combined with cervical cytology could reduce the referral rate to colposcopy.

Risk of malignancy in women who underwent hysterectomy for uterine prolapse

To evaluate the risk of missing a malignancy in surgical specimens following hysterectomy for uterine prolapse if routine pathological examination is not performed. Additionally, information on the risk of missing an hitherto unsuspected malignancy if uterine preservation is the preferred management option will be provided. A retrospective study was performed on all cases of surgery performed for uterine prolapse in a tertiary referral institution from 2003 to 2011. Those with confirmed malignancy before operation were excluded. The study subjects had their clinical history, investigations, the type of operations and histopathology report analysed. They were classified into symptomatic or asymptomatic, depending on whether they reported symptoms that were suggestive of uterine malignancy. A total of 640 women were studied. Three cases of hitherto unsuspected uterine malignancy were found, giving an incidence of 0.47%. Among the 456 asymptomatic women, both pre- and postmenopausal, the risk of incidental malignancy was 0.22%. Within the postmenopausal group, risk of incidental malignancy was 0.26%. Another 3 cases of uterine premalignant conditions were identified, giving an overall risk of premalignant and malignant uterine condition of 0.94%. Five cases of cervical intra-epithelial neoplasia were found, contributing to a risk of 0.78%. The risk of missing an uterine malignancy in patients with uterine prolapse is low if appropriate investigations are carried out prior to surgery. If hysterectomy is to be performed, we recommend that all surgical specimens be subjected to histopathological examination.

A cocktail of MCM2 and TOP2A, p16 INK4a and Ki-67 as biomarkers for the improved diagnosis of cervical intraepithelial lesion

The purpose of this paper was to explore the immunohistochemistry (IHC) results for a cocktail of minichromosome maintenance protein 2 (MCM2) and topoisomerase II (TOP2A), p16INK4a and Ki-67 as biomarkers for the diagnosis of cervical intraepithelial neoplasia (CIN), improving the routine interpretation of cervical histopathology. 133 cases of CIN were collected from the archival data. All routine hematoxylin and eosin (HE)-stained slides of the subjects were re-examined independently by three senior pathologists, to provide a "consensus diagnosis". Immunohistochemistry for the three biomarkers was performed, and the results were reviewed independently of the corresponding archival diagnosis to make a "diagnosis assisted by IHC" by the original pathological practitioners. The diagnosis accordance rate of the archival original diagnosis with the "consensus diagnosis" and the "diagnosis assisted by IHC" with the "consensus diagnosis" were verified by Fisher's exact test. The results showed that raw agreement between the original HE diagnosis and the "consensus diagnosis" was 88.55%, and raw agreement between the "diagnosis assisted by IHC" and the "consensus diagnosis" was 95.78%. The latter was significantly higher than the former (Fisher's exact test, p = 0.023). In conclusion, the three biomarkers had a high degree of sensitivity and specificity, and appear to be a useful and reliable diagnostic adjunct to improve the routine diagnosis, and reduce inter-observer variability in cervical biopsy specimens.

Cyclin D1, E‐cadherin and beta‐catenin expression in FIGO Stage IA cervical squamous carcinoma: diagnostic value and evidence for epithelial–mesenchymal transition

Immunohistochemistry is helpful in distinguishing cervical neoplastic lesions from their histological mimics, but has contributed less towards the sometimes problematic distinction of in-situ and superficially invasive tumours. Epithelial-mesenchymal transition (EMT) may be a mechanism of invasion in cervical neoplasia and expression of EMT-associated proteins could prove useful in this diagnostic setting. Immunohistochemical expression of cyclin D1, E-cadherin and beta-catenin was assessed in 22 biopsy specimens from FIGO Stage IA cervical squamous carcinomas, all of which also included foci of cervical intraepithelial neoplasia (CIN) 3, nine biopsies of CIN 3 adjacent to carcinoma, and 10 cases of CIN 3 only. Most invasive tumour cells expressed cyclin D1 and showed a reduction in E-cadherin and beta-catenin staining. Nuclear beta-catenin expression was not observed. Cyclin D1 staining was reduced or showed altered distribution in most cases of CIN 3, while adhesion protein expression generally was preserved. However, altered protein expression similar to that of invasion was seen in some CIN lesions. Most superficially invasive cervical squamous carcinomas show immunophenotypical changes consistent with EMT. These alterations, particularly cyclin D1 expression, may be useful diagnostically. Similar changes in CIN 3 lesions may indicate the acquisition of increased invasive potential.

Cost effectiveness of human papillomavirus test of cure after treatment for cervical intraepithelial neoplasia in England: economic analysis from NHS Sentinel Sites Study

Objectives To evaluate the cost effectiveness of human papillomavirus testing after treatment for cervical intraepithelial neoplasia (CIN).Design Economic analysis using a Markov modelling approach to combine cost and epidemiological data...

Clinical Validation of a Type-Specific Real-Time Quantitative Human Papillomavirus PCR against the Performance of Hybrid Capture 2 for the Purpose of Cervical Cancer Screening

To be acceptable for use in cervical cancer screening, a new assay that detects DNA of high-risk human papillomavirus (hrHPV) types must demonstrate high reproducibility and performance not inferior to that of a clinically validated HPV test. In the present study, a real-time quantitative PCR (qPCR) assay targeting the E6 and E7 genes of hrHPV was compared with Hybrid Capture 2 (hc2) in a Belgian cervical cancer screening setting. In women >30 years old, the sensitivity and specificity for intraepithelial neoplasias of grade 2 or worse (93 cases of cervical intraepithelial neoplasias of grade 2 or worse (CIN2+) and 1,207 cases of no CIN or CIN1) were 93.6% and 95.6%, respectively, and those of hc2 were 83.9% and 94.5%, respectively {relative sensitivity of qPCR/hc2 = 1.12 [95% confidence interval (CI), 1.01 to 1.23]; relative specificity = 1.01 [95% CI, 0.99 to 1.03]}. A score test showed that the sensitivity (P < 0.0001) and specificity (P < 0.0001) of the qPCR assay were not inferior to those of hc2 at the required thresholds of 90% and 98%, respectively. The overall agreement of hrHPV positivity between the two runs of the qPCR tests was 98.7% (95% CI, 97.5 to 99.4%), with a kappa value of 0.96 (95% CI, 0.83 to 1.00). The qPCR assay used in this study can be considered a reliable HPV assay that fulfills the clinical validation criteria defined for use in cervical cancer screening.

Expression of tight and adherens junction proteins in cervical neoplasia

ABSTRACTAdherens junctions (AJ) and tight junctions (TJ) play a key role in maintaining the apical-basolateral polarity and cohesive structure of epithelial cells. These epithelial junctions are maintained by the interaction of several key proteins including E-cadherin, claudins, occludin and zona-occludens. The zinc finger protein, Snail, has previously been identified as a possible regulator of several of these AJ and TJ proteins. Expression levels of ZO-1, occludin, claudins, E-cadherin, human Scribble protein and Snail were determined in HeLa and CaSki cervical carcinoma cell lines by imuunohistochemistry (IHC) and Western blotting. In tandem, tissue microarrays were utilised in the IHC-based detection of E-cadherin in 26 cases of non-cancerous cervical tissue, 15 cases of cervical intraepithelial neoplasia 1 (CIN1), 11 cases of CIN2, 12 cases of CIN3, 50 cases of squamous cell carcinoma and two cases of adenocarcinoma. This study found aberrant E-cadherin expression in CIN lesions and cases of squamous cell carcinoma compared to normal epithelium. HeLa cells were E-cadherin-negative while CaSki cells were positive, with HeLa cells showing a high level of Snail expression. Occludin and ZO-1 expression was detected in both cell lines. No expression was observed for claudin 1 or claudin 5 tight junction proteins in HeLa cells or CaSki cells. Loss of expression of claudin 1, claudin 5 and E-cadherin, with concomitant increase in Snail may be associated with loss of epithelial cell polarity and alterations in intercellular adhesion.

Human Papillomavirus Genotypes and Cofactors Causing Cervical Intraepithelial Neoplasia and Cervical Cancer in Korean Women

Infection with human papillomavirus (HPV) is a necessary cause of cervical cancer, but the risk associated with the various viral types and related cofactors have not been adequately assessed in Korean women. This study aimed to investigate the genotype distribution of HPV and cofactors related to cervical carcinogenesis in Korean women. We conducted a hospital-based case-control study in 215 women with histologically confirmed cervical neoplasia (111 cases of cervical intraepithelial neoplasia [CIN] and 104 cases of invasive cervical cancer [ICC]) and 1214 healthy control women. Polymerase chain reaction-based dot blot assays were used for detection of 16 high-risk HPV types. To clarify the cofactors, we administered questionnaires evaluating smoking, drinking, and sexual and reproductive history from women infected with HPV. Human papillomavirus was detected in 86.5% of the women with CIN and 96.2% of the women with ICC compared to 14.6% of the control women. The most common HPV types were, in descending order of frequency, types 16, 58, 18, 33, and 66 for CIN, and types 16, 18, 31, and 33 for ICC. Among the control women, HPV 16, 66, 33, 58, 18, and 31 were the most common types. Smoking and higher number of births (≥3) were associated with CIN (odds ratio [OR], 2.49; 95% confidence interval [CI], 1.21-5.15, and OR, 2.67; 95% CI, 1.36-5.28, respectively). This relationship was also found in the women with ICC (OR, 3.42; 95% CI, 1.59-7.38, and OR, 2.17; 95% CI, 1.08-4.38, respectively) compared to controls. In addition, the circumcision of sexual partner and the sexual habit of condom use were protective factors for ICC (OR, 0.47; 95% CI, 0.24-0.90, and OR, 0.19; 95% CI, 0.06-0.57, respectively). Human papillomavirus types 16, 18, 31, 33, and 58 are the major causative genotypes for cervical carcinogenesis in Korean women. Smoking and multiparity seem to be the most significant cofactors.

Is There a Role for Cervicography in the Detection of Premalignant Lesions of the Uterine Cervix?

This study aimed to compare cervical cancer screening by cervicography with screening by Pap test. This was a comparative multicenter study of cervical cytology and cervicography. The cervicography (slides of the cervix) was taken after the Pap test was completed. In total, samples were collected from 1176 patients. Colposcopy with biopsy was considered the gold standard for the final diagnosis of lesions observed by the Pap test and cervicography. Statistical analysis was performed using the binomial test. In cases in which the Pap test was negative for cervical lesions, diagnosis by cervicography was positive in 15 cases of cervical intraepithelial neoplasia 1 (CIN 1) (p = .00052), in 1 case of CIN 2, in 1 case of CIN 3, and in 1 case of cancer. However, cervicography produced 3 false-positive results (p < .0001). Cervicography may be used as a complementary screening method to the Pap test for cervical cancer.

Evaluation of p16INk4a, pRb, p53 and Ki-67 expression in cervical squamous neoplasia

Prior studies of p16 INK4a , pRb, p53 and Ki-67 expression have suggested that these markers may be preferentially expressed in cervical neoplasms. The purpose of this study was to assess the expression and the clinical significance of p16 INK4a, pRb, p53 and Ki-67 proteins in the cervical lesions. We obtained 106 cases with various categories of cervical squamous mucosa including squamous cell carcinoma (n=35), cervical intraepithelial neoplasia (CIN) II/III (n=26), CIN I (n=10), squamous metaplasia (n=15) and normal squamous mucosa (n=20). Immunohistochemical staining was performed for p16 INK4a , pRb, p53 and Ki-67 proteins in formalin-fixed and paraffin-embedded tissue sections of the uterine cervix. The evaluation of the immunohistochemical staining based on the frequencies of the expression and the mean immunoreactivity scores (IS) in each diagnostic category. p16 INK4a staining was detected in 26 of 35 cases (74.3%) of squamous cell carcinoma, in 16 of 26 cases (61.5%) of CIN II/III, in 6 of 10 cases (60%) of CIN I, in 9 of 15 cases (60%) of squamous metaplasia and negative in normal squamous mucosa. pRb expression was detected in all diagnostic categories; however, the proportion of pRb positive cells was relatively decreased in CIN II/III (38.5%) and squamous cell carcinomas (51.4%) compared to normal squamous epithelium (90%) and squamous metaplasia (73.3%). There were no significant differences in the expression of p53 in all diagnostic categories. Ki-67 expression was increased in squamous cell carcinoma (37.1%), CIN II/III (42.3%), CIN I (40%), but negative in squamous metaplasia and normal mucosa. In 35 cases of squamous cell carcinomas, multivariate analysis revealed no differences in p16 INK4a , pRb, p53, and Ki-67 expression according to the age of the patient, lymph node metastasis and the clinical stage. In conclusion, the combined use of p16 INK4a and Ki-67 immunoreactivity could improve the diagnostic specificity of squamous cell carcinoma of uterine cervix.

Only a Small Fraction of High-Grade Cervical Lesions Are Discovered After an Interpretation of Atypical Squamous Cells of Undetermined Significance When Using Imager-Assisted, Liquid-Based Papanicolaou Tests and the Bethesda 2001 System

Previous work has reported that most high-grade cervical neoplasia is seen in patients with preceding Papanicolaou test results of atypical squamous cells of undetermined significance. This information was based on conventional test results and the Bethesda 1991 reporting system and was determined before the current treatment guidelines. Our objective was to perform a retrospective review of all histologically confirmed, high-grade cervical neoplasia to determine the diagnosis of the preceding liquid-based Papanicolaou test. A total of 189 histologically confirmed, high-grade cervical intraepithelial neoplasia (CIN) cases grade 2 and greater were identified for a 1-year period. Of the 189 cases, 10 (5.3%) had a previous diagnosis of atypical squamous cells of undetermined significance; 55 (29.1%) had low-grade squamous intraepithelial lesions; 31 (16.4%) had low-grade squamous intraepithelial lesions, unable to rule out a high-grade squamous intraepithelial lesion; 21 (11.1%) had atypical squamous cells, unable to rule out a high-grade squamous intraepithelial lesion; 68 (36%) had high-grade squamous intraepithelial lesions; 1 (0.5%) had atypical glandular cells; 1 (0.5%) had adenocarcinoma in situ; and 2 (1%) had invasive carcinoma. Combined "low grade" Papanicolaou test results (atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion) preceded 51 of 103 cases of CIN 2 (49.5%) and 14 of 103 cases (13.6%) of CIN 3/cancer, whereas "high grade" Papanicolaou test results (atypical squamous cells, unable to rule out a high-grade squamous intraepithelial lesion; low-grade squamous intraepithelial lesions, unable to rule out a high-grade squamous intraepithelial lesion; high-grade squamous intraepithelial lesions; atypical glandular cells; adenocarcinoma in situ; and invasive carcinoma) preceded 52 of 103 CIN 2 cases (50.5%) and 72 of 103 CIN 3/cancer cases (69.9%). Our data show that we can now more-reliably predict high-grade dysplasia on routine Papanicolaou tests. Only a small fraction of histologically confirmed CIN 2/3 cases are found following a Papanicolaou test diagnosis of atypical squamous cells of undetermined significance.

Altered expression levels of HLA class II and costimulatory molecules on circulating monocytes from patients with cervical intraepithelial neoplasia and squamous cervical cancer

The aim of this study was to investigate the role of the cell surface expression levels of HLA class I and II molecules, the costimulatory molecules CD80/B7-1 and CD86/B7-2, and the adhesion molecules CD54 and CD58 during cervical carcinogenesis. The expression levels of MHC classIandII molecules, the costimulatory molecules CD80/B7-1 and CD86/B7-2 and the adhesion molecules CD54 and CD58 on CD14+ peripheral blood monocytes (PBMs) from 21cases of cervical intraepithelial neoplasia (CIN) II-III, 51 squamous cervical carcinomas (SCCs) and 18healthy controls were analyzed using flow cytometry analysis. We found increased expression levels of HLA-DR (p=0.000), HLA-DQ (p=0.000), CD86/B7-2 (p=0.002) and CD58 (p=0.000) on PBMs from patients with SCC and CINII-III, compared with healthy control subjects, whereas no significant difference existed in the expression levels of HLA class I antigens, HLA-DP CD80/B7-1 and CD54. Upregulated expression levels of HLA-DR, HLA-DQ, CD86/B7-2 and CD58 were associated with disease progression, indicating that an increased expression of HLA-DR, HLA-DQ, CD86/B7-2 and CD58 on PBMs may be correlated with the evolution of cervical cancer.